Since chemical carcinogens are known to cause chromosomal aberrations, alter DNA dependent RNA synthesis, and activate latent viral genes incorporated into host cell chromosomes, it is proposed that the carcinogens mediate all or part of the action on cells at the level of chromatin. Within minutes after IP injection of labelled carcinogens into rats or application of these compounds to cells in culture, there is a noticeable uptake by the cells with radioactivity immediately associated with cytoplasmic proteins and nuclei. As much as 90% of the total nuclear binding is associated with isolated chromatin. Recent studies in this laboratory have demonstrated the presence of specific high affinity binding site for chemical carcinogens in the transcriptionally active fraction of the chromosomal material in mouse embryo cells. Further studies suggest that the more potent carcinogenic polycyclic aromatic hydrocarbons display a much greater affinity for these sites then the noncarcinogenic compounds. In addition, this binding represents both noncovalent and covalent binding. The latter is metabolically dependent. It is planned to more thoroughly ascertain the specificity of this binding site for carcinogenic compounds, to determine whether or not these sites are present in cells which are resistant to transformation, to determine whether or not these specific sites are found in certain organs of mice, to isolate and characterize the chromosomal component to which these carcinogens are bound, and to ascertain the exact structure of metabolites of the parent hydrocarbons which are bound to the chromosomal material. These latter studies will be undertaken using high speed liquid chromatography and mass spectrometry. Emphasis are being placed on the possible similarities or dissimilarities that methyl-cholanthrene and benzo(a)pyrene have with steroid hormones with respect to cytoplasmic receptors, migration to the nucleus, and binding to chromatin. BIBLIOGRAPHIC REFERENCE: Spelsberg, T.C.,Stake, E., and Witzke, D.: Fractionation of Chromosomal Nonhistone Proteins Using Chromatin Cellulose Resins: Purification of Steroid Hormone Binding Proteins. Methods in Enzymol. 1977, in press.